It has been reported that the reflectance of the retinal nerve fiber layer (RNFL) may change prior to, or concurrent with, RNFL thinning in glaucoma. It has also been reported that hypodense holes in the RNFL may be a manifestation of glaucomatous neuropathy. This led us to hypothesize that reductions in RNFL reflectance intensity recorded by optical coherence tomography (OCT) may be observed in human glaucoma, and may provide useful additional information beyond RNFL thickness.

Methods

Participants enrolled in an ongoing longitudinal study of glaucomatous progression had peripapillary circle scans acquired using Spectralis OCT (Heidelberg Engineering), and performed perimetry (HFA 24-2, Carl Zeiss Meditec), every six months. Data were analyzed from the most recent seven visits with reliable perimetry and acceptable quality OCT results, from 369 eyes of 190 individuals. RNFL intensities were normalized to reduce the effect of inter-session signal strength variation. For each circle scan, the intensity ratio was defined as the mean intensity of pixels within the delineated RNFL divided by the mean intensity of pixels between the outer boundary of the RNFL and Bruch’s Membrane. Mean RNFL thickness, and Mean Deviation (MD) from perimetry, were also recorded. For each of the three parameters, linear regression was used to find the rate of change over time. A generalized estimating equation model was then used to predict the rate of MD change from the rates of change of the structural measures accounting for inter-eye correlations.

Results

Mean rates were -0.17±0.36dB/yr for MD, -0.81±1.42µm/yr for RNFLT, and -0.02±0.26yr-1 for intensity ratio. In a bivariate model, MD rate was predicted by RNFLT rate (p=0.00003) and the interaction between RNFLT rate and intensity ratio rate (p=0.0307). For an eye with an RNFLT rate equal to the mean in the cohort, if the intensity ratio decreased at the fastest observed rate then the predicted MD rate would be -0.20dB/yr. For the same mean RNFLT rate, if the intensity ratio increased at the fastest observed rate then the predicted MD rate would be -0.09dB/yr.

Conclusions

More rapid reduction of RNFL reflectance intensity over time is associated with a more rapid rate of visual field deterioration, for the same rate of RNFL thinning. While these are early results, they suggest potential improvements to the interpretation and quantification of OCT scans.